Exploiting Interfacial Design for the Electrocatalytic Construction of C-C bonds

利用界面设计电催化构建 C-C 键

• 批准号: 10713693
• 负责人: Anna Wuttig
• 金额: $ 34.41万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713693
• 关键词: Adopted; Adoption; Alcohols; Aldehydes; Chemicals; Complex; Coupling; Disease; Electricity; Electrodes; Elements; Generations; Ketones; Medicine; Methods; Pharmacologic Substance; Preparation; Property; Reaction; Research; Solid; design; drug development; drug discovery; forging; functional group; improved; interfacial; prevent; programs

PROJECT ABSTRACT The objective of our research is to access new chemical spaces in drug discovery and development by reimagining the catalytic conditions for electricity-driven organic transformations. We propose a synthetic platform to couple every major class of C(sp3) organic halide electrophile with aldehyde and ketones. By fine- tuning the key electrophile interactions with the electrode material by interfacial design, we propose to forge C(sp3)–C(sp3) bonds with high selectivity and stereoselectivity. Our approach will provide direct and catalytic access to new chiral alcohol and α,α-difluorobenzylic derivatives, prevalent motifs in several high-profile pharmaceuticals, from accessible feedstocks. Our synthetic methods will provide complementary and direct approaches to access (enantio)selective C(sp3)–C(sp3) bonds that are restricted to non-catalytic or multi-step reactions. Non-catalytic reactions require either the generation of highly reactive reaction intermediates that degrade bioactive functional groups or the use of expensive and rare elements that limit wide-spread adoption. In addition to increasing the accessibility to prepare and diversify pharmaceuticals via electrocatalytic C(sp3)– C(sp3) bond formation, our mechanistic and structural analyses of electrified interfaces will dissect the fundamental properties that control interfacial reactivity in complex electrosynthetic manifolds. Thus, our program will reveal how new mechanisms to construct C(sp3)–C(sp3) can be accessed by engaging a recoverable and infinitely reusable solid electrocatalyst interface; an inherently sustainable synthetic approach that can be readily adoptable by medicinal chemists.

项目摘要 我们的研究目标是通过以下方式在药物发现和开发中获得新的化学空间： 重新设想电驱动有机转化的催化条件。我们提出了一种合成的 该平台用于将每种主要类别的C（sp3）有机卤化物亲电试剂与醛和酮偶联。通过罚款- 通过界面设计调整与电极材料的关键亲电相互作用，我们建议锻造 C（sp3）-C（sp3）键具有高选择性和立体选择性。我们的方法将提供直接和催化 获得新的手性醇和α，α-二氟苄基衍生物，在几个高姿态普遍图案 制药，从可获得的原料。我们的合成方法将提供互补和直接的 获得（对映体）选择性C（sp3）-C（sp3）键的方法限于非催化或多步 反应.非催化反应需要产生高活性反应中间体， 降解生物活性官能团或使用昂贵和稀有的元素，限制了广泛采用。 除了增加通过电催化C（sp3）制备和多样化药物的可及性之外， C（sp3）键的形成，我们对带电界面的机理和结构分析将剖析 控制复杂电合成歧管中界面反应的基本性质。因此，我们的计划 将揭示如何构建C（sp3）-C（sp3）的新机制可以通过参与可恢复和 无限可重复使用的固体电催化剂界面;一种固有的可持续合成方法， 被药物化学家采用。